We showed previously that pretreatment of butyrate, which is an endogenous histone deacetylase (HDAC) inhibitor normally fermented from undigested fiber by intestinal microflora, seriously alleviated ischemia reperfusion (I/R)-induced liver injury by inhibiting the nuclear factor κB (NF-κB) pathway. The goal of this study was to investigate the effect of butyrate administrated at the onset of ischemia for HDAC inhibition in hepatic I/R injury. Sprague Dawley rats were subjected to warm ischemia for 60 min followed by 6 and 24 h of reperfusion. Butyrate was administrated at the onset of ischemia. Liver injury was evaluated by serum levels of aminotransferase, inflammatory factors, and histopathology. The levels of acetylated histone H3 and expression of heat shock protein (Hsp) 70 were measured by Western blot. After reperfusion, the levels of acetylated histone H3 significantly decreased. Butyrate treatment markedly prevented the reduction of acetylated histone H3 and upregulated the expression of Hsp70, thereby reducing liver injury. Our study demonstrated that I/R resulted in marked reduction of histone acetylation; butyrate exerted a great hepatoprotective effect through HDAC inhibition and Hsp70 induction.

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So Butyrate will be added to the list of Supplements that induce HSP-70 along with Resveratrol, Curcumin, TUDCA and Selenium which are a main part of this regimen.

My question is : Is it possible to bring homeostasis (and treat CFS) just by supplementing with Clostridium Butyricum?

Perhaps some sufferers will feel great just with this Supplement and others may need the extra boost of HSP-70 from supplements such as TUDCA, Resveratrol, etc.

My question is : Is it possible to bring homeostasis (and treat CFS) just by supplementing with Clostridium Butyricum?

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It might not be enough, or you might not need it at all. First of all, you need fibers, resistant starch in particular, which are fermented into SCFAs, including butyrate. But if your clostridia species are decimated by antibiotics for example, you will not be able to create enough butyrate, and in that case taking CB could help.

You might be interested in looking at this resistant starch primer, by @Gestalt :

It might not be enough, or you might not need it at all. First of all, you need fibers, resistant starch in particular, which are fermented into SCFAs, including butyrate. But if your clostridia species are decimated by antibiotics for example, you will not be able to create enough butyrate, and in that case taking CB could help.

You might be interested in looking at this resistant starch primer, by @Gestalt :

This pilot investigation demonstrated that the CFS, PGI and FM subjects had a significant overlap between their syndromes. Despite the differences in their original case designations, they had very similar responses on questionnaire, quality of life and nociceptive measures. Again, despite the differences in the diagnostic label applied to them for study entry, their cerebrospinal fluid proteomes demonstrated reproducible constituents. The CFS-related proteome was essentially the same for the two independent CFS cohorts. The proteome was remarkable for the number of proteins associated with protein misfolding and cerebrovascular amyloidosis syndromes.
These included gelsolin, amyloid β protein (APLP1), Igλ ,C3, C4, chromogranin B,α2-macroglobulin and α 1-antichymotrypsin antiproteases, the heme and iron scavengers haptoglobin, hemopexin, and orosomucoid 2, angiogenic and antiangiogenic prohormones such as autotaxin and PEDF, and the structural proteins gelsolin, BEHAB and keratin 16. Their presence in the CFS – associated proteome suggested a potential pathophysiological link. We propose the hypothesis that CFS may be a nonlethal, protein – misfolding, cerebrovascular amyloidosis –like syndrome.

The hypothesis that amyloid pathology precedes and induces the tau pathology of Alzheimer's disease is experimentally supported here through the identification of GSK-3 isozymes as a major link in the signaling pathway from amyloid to tau pathology. This study compares two novel bigenic mouse models: APP-V717I x Tau-P301L mice with combined amyloid and tau pathology and GSK-3beta x Tau-P301L mice with tauopathy only. Extensive and remarkable parallels were observed between these strains including 1) aggravation of tauopathy with highly fibrillar tangles in the hippocampus and cortex; 2) prolonged survival correlated to alleviated brainstem tauopathy; 3) development of severe cognitive and behavioral defects in young adults before the onset of amyloid deposition or tauopathy; and 4) presence of pathological phospho-epitopes of tau, including the characteristic GSK-3beta motif at S396/S404. Both GSK-3 isozymes were activated in the brain of parental APP-V717I amyloid mice, even at a young age when cognitive and behavioral defects are evident but before amyloid deposition. The data indicate that amyloid induces tauopathy through activation of GSK-3 and suggest a role for the kinase in maintaining the functional integrity of adult neurons.

The deposition of amyloid-β (Aβ) peptides in senile plaques is one of pathological hallmarks of Alzheimer's disease (AD). Mitochondrial dysfunction is an early event of cell apoptosis. Increasing evidence indicates that Aβ induces neuronal apoptosis through mitochondrial dysfunction. Curcumin, an anti-oxidative component of turmeric (Curcuma longa), has shown anti-tumor, anti-inflammatory, and anti-oxidative properties. In this study, we investigated the protective effects of curcumin against mitochondrial dysfunction induced by Aβ. Based on the assay results of mitochondrial metabolic markers, we found that curcumin protects human neuroblastoma SH-SY5Y cells against the Aβ-induced damage of mitochondrial energy metabolism. Curcumin inhibits Aβ-induced mitochondrial depolarization of membrane potential (Δψm) and suppresses mitochondrial apoptosis-related proteins including cytochrome c, caspase-3, and Bax, which are activated by Aβ. Aβ-induced disturbances of redox state are linked to mitochondrial dysfunction. Curcumin normalizes cellular antioxidant enzymes (including SOD and catalase) in both protein expression and activity and decreases oxidative stress level in Aβ-treated cells. Both total GSK-3β expression and phospho-Ser9 GSK-3β (pSer9-GSK-3β) are down-regulated in the cells pre-treated with curcumin. This study demonstrates curcumin-mediated neuroprotection against Aβ-induced mitochondrial metabolic deficiency and abnormal alteration of oxidative stress. Inhibition of GSK-3β is involved in the protection of curcumin against Aβ-induced mitochondrial dysfunction.

Resveratrol (trans-3, 5, 4'-trihydroxystilbene) is a polyphenolic phytoalexin known to exhibit antioxidant and neuroprotective effects in several experimental models. Amyloid β peptide (Aβ), a core component of extracellular senile plaques accumulates in the brains of patients with Alzheimer's disease and is related to the development of cognitive impairment and neuronal loss. The present study evaluates the neuroprotective action of resveratrol on Aβ-induced oxidative stress and memory loss. Cultured rat hippocampal H19-7 neuronal cell line was pretreated with 75 μM of resveratrol for 2 hrs followed by 25 μM of Aβ (1-40) for 24 hrs. H19-7 cells treated with Aβ exhibited increased lipid peroxide levels. Enzymatic antioxidants including superoxide dismutase, catalase, glutathione reductase, and non-enzymatic antioxidants such as tocopherol, ascorbic acid and glutathione were decreased in the Aβ treated group when compared to the control group. Aβ treatment also increased the expression of total tau as well as phosphorylated forms of tau (CP13, S202/205; PHF1, S396/404) and decreased the expression of insulin degrading enzyme (IDE), phosphoglycogen synthase kinase 3β involved in Aβ degradation and tau hyper phosphorylation. Expression of PSD-95 and Arc proteins, essential for synaptic maturity and plasticity, was decreased by Aβ treatment. Resveratrol treatment attenuated the accumulation of lipid peroxide levels, up-regulated the antioxidant activities and improved the expression of memory-associated proteins in Aβ treated H19-7 cells. These findings highlight the neuroprotective effect of resveratrol in preventing Aβ-induced oxidative damage and memory loss in vitro.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by accumulation of amyloid-β (Aβ) peptide in the hippocampus and frontal cortex of the brain, leading to progressive cognitive decline. The endogenous bile acid tauroursodeoxycholic acid (TUDCA) is a strong neuroprotective agent in several experimental models of disease, including neuronal exposure to Aβ. Nevertheless, the therapeutic role of TUDCA in AD pathology has not yet been ascertained. Here we report that feeding APP/PS1 double-transgenic mice with diet containing 0.4 % TUDCA for 6 months reduced accumulation of Aβ deposits in the brain, markedly ameliorating memory deficits. This was accompanied by reduced glial activation and neuronal integrity loss in TUDCA-fed APP/PS1 mice compared to untreated APP/PS1 mice. Furthermore, TUDCA regulated lipid-metabolism mediators involved in Aβ production and accumulation in the brains of transgenic mice. Overall amyloidogenic APP processing was reduced with TUDCA treatment, in association with, but not limited to, modulation of γ-secretase activity. Consequently, a significant decrease in Aβ(1-40) and Aβ(1-42) levels was observed in both hippocampus and frontal cortex of TUDCA-treated APP/PS1 mice, suggesting that chronic feeding of TUDCA interferes with Aβ production, possibly through the regulation of lipid-metabolism mediators associated with APP processing. These results highlight TUDCA as a potential therapeutic strategy for the prevention and treatment of AD.

@mariovitali: I'm interested in your theory, and bought some TUDCA to try. I either take daily or have on hand everything else in your regimen so will be putting it all together starting today. I'll let you know if I experience any benefits. I'm already doing pretty good from methylation and tweaking my gut, but am very concerned about liver support, since many of my problems seem to point to "liver congestion". I've put the poor thing through the wringer, for sure.

I have a couple/few questions for you.

Based your research, what's the amount of time we should wait to drink alcohol after stopping TUDCA? I don't drink much but very occasionally I take a glass or two, and will be taking a trip in the fall where I will probably be imbibing fairly heavily at least one night. It would be good to know.

Also I read that TUDCA during alcohol consump or after helps decrease liver damage, but TUDCA consumption before drinking may increase it. Based on what you know, is this true?

Finally, you say to stay away from L-carnitine. But I've found L-carnitine-fumarate to be a critical supplement in my recovery so far. Why do you say stay away from l-carnitine and does this include the fumarate form?

In looking at the directions and product warnings on my bottle of TUDCA, I note that it says: "Do not use for more than 30 days without a 90 day break." Of course, as a dietary supplement, the same bottle recommends taking one capsule four times a day, while @mariovitali seems to be advocating only 2 capsules per day. Anyone have any theories as to why they'd include this "warning"?

Bingo! Please do not confuse crocin with an acetaminophen product. Tylenol produces oxidative stress -- not eliminates it. Saffron and Gardenia are herbs that contain high amounts of crocin. Gardenia is a better, cheaper choice since it also contains crocetin, another Xanthophyll Carotenoid.

Regarding alcohol consumption, i do not know what is the amount of time that has to pass in order to drink. I just do not drink at all (unfortunately) but i will start soon once i stop TUDCA.

L-Carnitine could be beneficial but for a person who had the Post-Finasteride Syndrome such as me, it wasn't good. Perhaps now it is. The same applies for D-Limonene which is a potent P450 Induction and anti-Inflammatory agent (but it is a potent HmG-CoA Inhibitor).

It may well be a fact that CFS Sufferers do not have any problem taking foods/supplements which are HmG-CoA inhibitors so i will reflect that to my original post.

Usage of 500mg TUDCA daily for one year (in persons after liver transplants) was not associated with any adverse effects[64] and in otherwise healthy obese persons doses of 1,750mg have been well tolerated for up to 4 weeks.[55]

In persons with primary biliary cirrhosis, 750mg daily for 2 months was not associated with any adverse effects[3] and a similar population was able to tolerate 1,500mg daily for 6 months with no adverse effects.[4]

9.2. Other
Infusion studies find that rates of TUDCA infusion from 4-32umol/kg/min are not associated with any abnormal liver histological findings.[25]

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I am taking 500 mg for about 2 months now and i am planning to stop it. I have no idea why they used this warning.

@all

Also, for us with PFS it is beneficial to upregulate SRD5A3 through Spinach Consumption. Spinach contains Dolichols which is a product of Mevalonate Pathway and N-Linked Glycosylation. N-Linked Glycosylation is very important for proper Protein Folding.

What i am trying to say here is that quite possibly we all arrived (=Finasteride Users, Accutane Users and CFS Sufferers) in this situation from a different route...but the mechanism behind our problems is Protein Misfolding and ER Stress.

I have been taking antihistamines lately, and feeling worse. So I did a little searching:

Interesting studies from Varadarajan et al. [28] have uncovered a new cellular stress response characterized by a striking, but reversible, reorganization of ER membranes that occurs independently of the UPR, resulting in impaired ER transport and function that culminates in cell death. ER membrane aggregation was regulated, in part, by anti-apoptotic Bcl-2 family members, particularly Mcl-1. Using connectivity mapping, they reported the widespread occurrence of this stress response by identifying several structurally diverse chemicals from different pharmacological classes, including antihistamines, antimalarials, and antipsychotics, which induce ER membrane reorganization. Furthermore, they demonstrated that ER membrane aggregation can result in pathological consequences.

On the other hand, fexofenadine (an antihistamine) suppressed ER stress:

Fexofenadine significantly inhibited the upregulated expression of IL-8 in HCT116 and COLO205 cells stimulated with TNF-α. Fexofenadine suppressed NF-κB DNA binding activity. CHOP mRNA expression was enhanced in the presence of TNF-α, and it was dampened by pretreatment of fexofenadine. In addition, the induction of ER stress markers caspase-12 and p-eIF2-α were significantly suppressed by the pretreatment of fexofenadine.

Anecdotally, fexofenadine (Allegra) can have a very mild stimulating effect in some people that might be helpfulful. (I'm not referring here to the paradoxical-type, uncomfortable stimulating effects that some H1 antihistamines can sometimes have.)

Although that anecdotal stimulating effect didn't hold up in this study here:

I do find fexofenadine to be very slightly stimulating, although at 1/4 the usual 24 hr dose. Any higher amount feels tiring, though. Note that fexofenadine uses the p-glycoprotein transporter (gene = ABCB1; see my signature), and so sensitivity to dosing can be partly related to that. (Ranitidine/Zantac uses that transporter as well.)

It's funny about the study above, because methylphenidate (Ritalin) and modafinil (Provigil) both put me to sleep. But just to emphasize, the stimulating effect that fexofenadine might have in some people is generally only very mild.

Yeah, that's one of the most frustrating things about a forum like this. So much valuable information is scattered all over numerous message threads that it's very hard to get a handle on it. There must be some better method to aggregate all this information in some dynamic manner.

Yeah, that's one of the most frustrating things about a forum like this. So much valuable information is scattered all over numerous message threads that it's very hard to get a handle on it. There must be some better method to aggregate all this information in some dynamic manner.

This technology essentially extracts Topics out of Text. I would be more than happy to deploy this solution to Phoenix Rising Data -Free of Charge- with the hope of extracting Knowledge out of the Thousands of Conversations.